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view-id-bmj_rapid_responses view-display-id-bmj_rr_article view-dom-id-5f1339c754c77ff77a2beb7d25020b25\u0022\u003E\n \u003Cdiv class=\u0022view-header\u0022\u003E\n \u003Cdiv id=\u0022response-header-description\u0022\u003ERapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. \u003Cem\u003EThe BMJ\u003C\/em\u003E reserves the right to remove responses which are being wilfully misrepresented as published articles.\u003C\/div\u003E \u003C\/div\u003E\n \n \u003Cdiv class=\u0022view-filters\u0022\u003E\n \u003Cform action=\u0022\/\u0022 method=\u0022get\u0022 id=\u0022views-exposed-form-bmj-rapid-responses-bmj-rr-article\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cdiv\u003E\u003Cdiv class=\u0022views-exposed-form\u0022\u003E\n \u003Cdiv class=\u0022views-exposed-widgets clearfix\u0022\u003E\n \u003Cdiv class=\u0022views-exposed-widget views-widget-sort-by\u0022\u003E\n \u003Cdiv class=\u0022form-type-select form-item-sort-by form-item form-group\u0022\u003E\n \u003Clabel for=\u0022edit-sort-by\u0022\u003ESort by \u003C\/label\u003E\n \u003Cselect class=\u0022form-control form-select\u0022 id=\u0022edit-sort-by\u0022 name=\u0022sort_by\u0022\u003E\u003Coption value=\u0022field_highwire_a_epubdate_value\u0022 selected=\u0022selected\u0022\u003EDate Published\u003C\/option\u003E\u003C\/select\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-exposed-widget views-widget-sort-order\u0022\u003E\n \u003Cdiv class=\u0022form-type-select form-item-sort-order form-item form-group\u0022\u003E\n \u003Clabel for=\u0022edit-sort-order\u0022\u003EOrder \u003C\/label\u003E\n \u003Cselect class=\u0022form-control form-select\u0022 id=\u0022edit-sort-order\u0022 name=\u0022sort_order\u0022\u003E\u003Coption value=\u0022ASC\u0022\u003EAscending\u003C\/option\u003E\u003Coption value=\u0022DESC\u0022 selected=\u0022selected\u0022\u003EDescending\u003C\/option\u003E\u003C\/select\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-exposed-widget views-widget-per-page\u0022\u003E\n \u003Cdiv class=\u0022form-type-select form-item-items-per-page form-item form-group\u0022\u003E\n \u003Clabel for=\u0022edit-items-per-page\u0022\u003EItems per page \u003C\/label\u003E\n \u003Cselect class=\u0022form-control form-select\u0022 id=\u0022edit-items-per-page\u0022 name=\u0022items_per_page\u0022\u003E\u003Coption value=\u00225\u0022\u003E5\u003C\/option\u003E\u003Coption value=\u002210\u0022 selected=\u0022selected\u0022\u003E10\u003C\/option\u003E\u003Coption value=\u002220\u0022\u003E20\u003C\/option\u003E\u003Coption value=\u002240\u0022\u003E40\u003C\/option\u003E\u003Coption value=\u002260\u0022\u003E60\u003C\/option\u003E\u003C\/select\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-exposed-widget views-submit-button\u0022\u003E\n \u003Cinput class=\u0022btn btn-info form-submit\u0022 type=\u0022submit\u0022 id=\u0022edit-submit-bmj-rapid-responses\u0022 name=\u0022\u0022 value=\u0022Apply\u0022 \/\u003E \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003C\/form\u003E \u003C\/div\u003E\n \n \n \u003Cdiv class=\u0022view-content\u0022\u003E\n \u003Cdiv class=\u0022views-row views-row-1 views-row-odd views-row-first\u0022\u003E\n \r\n\u003Cdiv class=\u0022node node-highwire-comment clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022row rr-header\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022rr-left-column\u0022 class=\u0022\u0022\u003E\r\n\r\n \r\n \u003Cdiv class=\u0022response-title\u0022\u003E\r\n \u003Ca href=\u0022\/content\/346\/bmj.f1325\/rr\/643408\u0022\u003E\u003Ch3\u003ERe: Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials\u003C\/h3\u003E\r\n \u003C\/a\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \r\n \r\n \u003Cdiv class=\u0022content\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022response-body\u0022\u003E\r\n \u003Cp\u003EHe and MacGregor distort our message. We do not claim that their analysis is similar to ours. On the contrary we emphasize the difference (167 references versus 30 references), but in spite of the difference the trends of the results are similar. The statistical differences may be due to differences in duration of treatment, or they may be due to statistical power. Furthermore, although blood pressure is associated with mortality, there is no evidence that sodium reduction reduces mortality mediated by a blood pressure reduction.\u003C\/p\u003E\n\u003Cp\u003EHe and MacGregor repeat their well known arguments. In that context they refer to their analysis in the Lancet (1). This analysis is biased. The primary analysis by Taylor et al. (2) was designed and then conducted according to the design. He and MacGregor reorganized the data to give a result in accordance with their view. At the same time they avoided making the same analysis on the all cause mortality data, although the all cause mortality data were complete (available in 7 of 7 studies) in contrast to the CVD data (available in 4 of 7 studies). A similar analysis on the all cause mortality outcome from all 7 studies (or the 6 studies excluding the heart failure study) shows no difference between the usual sodium group and the reduced sodium group. Further, it should be emphasized that all the included studies with the exception of the heart failure study reduce sodium to a level above the recommended level (2000-2300 mg). So there is no evidence (not even He and MacGregor\u2019s analysis) to prove beneficial effects on mortality of sodium reduction to a level below 2000 mg, which is the latest WHO recommendation, but there is non-optimal evidence in heart failure patients that a reduction below 2000 mg may be harmful. Concerning renin and aldosterone, these hormones increase slowly and linearly from 200 to 100 mmol of sodium, but below 100 mmol renin and aldosterone increase exponentially (3). A sodium intake below 100 mmol for the whole world\u2019s populations is the goal of He, MacGregor and WHO - without any evidence of the possible consequences.\u003C\/p\u003E\n\u003Cp\u003E1)\tHe FJ, MacGregor GA. Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials. Lancet 2011;378:380-2.\u003Cbr \/\u003E\n2)\tTaylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011;7:CD009217.\u003Cbr \/\u003E\n3)\tBrunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT, Krakoff LR, Bard RH, B\u00fchler FR.Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med. 1972 Mar 2;286(9):441-9.\u003C\/p\u003E\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-competing\u0022\u003E\r\n \u003Cp\u003E\u003Cstrong\u003ECompeting interests: \u003C\/strong\u003E\r\n No competing interests\u003C\/p\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \u003C\/div\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-right-column\u0022 class=\u0022\u0022\u003E\r\n \u003Cdiv class=\u0022response-date\u0022\u003E\r\n \u003Cstrong\u003E01 May 2013\u003C\/strong\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-author\u0022\u003E\r\n Niels Graudal \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-occupation\u0022\u003E\r\n Consultant \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-other_authors\u0022\u003E\r\n Gesche J\u00fcrgens \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-affiliation\u0022\u003E\r\n Copenhagen University Hospital \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-address\u0022\u003E\r\n Blegdamsvej 9, DK-2100 Copenhagen \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022twitter-address\u0022\u003E\r\n \u003Ca href=\u0022https:\/\/twitter.com\/\u0022\u003E\u003C\/a\u003E \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-links\u0022\u003E\r\n\r\n \r\n \r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-separator\u0022 class=\u0022clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022light-grey-line\u0022\u003E\u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n\u003C\/div\u003E\r\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-row views-row-2 views-row-even\u0022\u003E\n \r\n\u003Cdiv class=\u0022node node-highwire-comment clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022row rr-header\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022rr-left-column\u0022 class=\u0022\u0022\u003E\r\n\r\n \r\n \u003Cdiv class=\u0022response-title\u0022\u003E\r\n \u003Ca href=\u0022\/content\/346\/bmj.f1325\/rr\/641430\u0022\u003E\u003Ch3\u003ERe: Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials\u003C\/h3\u003E\r\n \u003C\/a\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \r\n \r\n \u003Cdiv class=\u0022content\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022response-body\u0022\u003E\r\n \u003Cp\u003EGraudal and J\u00fcrgens claim that our meta-analysis (1) is similar to theirs (2), however, this claim is wrong. Graudal and colleagues\u2019s meta-analysis included a large number of metabolic studies with many trials having a duration of only 5 days and the median duration of all of the studies in the normotensives was only 7 days. In addition, they included salt-loading trials where very large amounts of salt had been given, e.g. up to 20 g\/d and then reduced suddenly to less than 1 g\/d for only 5 days. These short-term metabolic studies are completely irrelevant to the public health recommendations for longer-term modest reductions in salt intake, yet Graudal and colleagues persist in drawing public health conclusions about the benefits of population salt reduction from these types of studies. Salt reduction, like blood pressure lowering drugs, takes time to work and all drug regulatory agencies require evidence that, for drugs lowering blood pressure, the trials must be for a month or ideally longer. It is well established that diuretics, which work in a similar way to salt restriction, take at least a month or longer, to have a maximum blood pressure lowering effect. \u003C\/p\u003E\n\u003Cp\u003EOur meta-analysis, in contrast to Graudal\u2019s, only included trials with a modest reduction in salt intake for at least 4 weeks, and is of public health relevance. These longer term modest reductions in salt intake of the same amount as the public health recommendations do lower blood pressure significantly in both hypertensive and normotensive individuals by amounts that are of great public health importance, given that blood pressure is the single biggest cause of death in the world (3,4). The risks start at blood pressure of 115\/75 mmHg (5) (i.e. over 80% of the UK adult population have blood pressure above this level). Our meta-analysis also showed that the greater the reduction in salt intake the greater the fall in blood pressure. \u003C\/p\u003E\n\u003Cp\u003EOur current meta-analysis (1) also has the following new findings: (a) 68% of the variance of the change in systolic blood pressure could be explained by four variables, i.e. age, ethnic group, blood pressure levels and the change in 24 hour urinary sodium; (b) the effects of salt reduction on systolic blood pressure are significant in both whites and blacks, men and women; (c) with a longer-term modest reduction in salt intake, there is only a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in adrenaline, cholesterol, low-density lipoprotein, high-density lipoprotein or triglycerides. In our view, the results of our meta-analysis provide strong further support for a reduction in population salt intake, which will lower population blood pressure and, therefore, reduce strokes, heart attacks and heart failure.\u003C\/p\u003E\n\u003Cp\u003EGraudal and J\u00fcrgens tried to imply that an increase in plasma renin activity and aldosterone with salt restriction is harmful. They do not seem to be aware that there is a reciprocal relationship between sodium balance and the renin-angiotensin-aldosterone system, and that with long term modest reductions in salt intake there are only very small increases in plasma renin activity and aldosterone, and this is an entirely normal physiological response to the changes in sodium balance. Indeed diuretics, which cause a small loss of sodium from the body and a reduction in sodium balance, also cause increases in plasma renin activity, angiotensin II and aldosterone, to a much greater extent than modest salt reduction. Diuretics have been demonstrated in outcome trials to reduce cardiovascular disease mortality in individuals with raised blood pressure (6). \u003C\/p\u003E\n\u003Cp\u003EGraudal and J\u00fcrgens also imply that salt reduction has deleterious effects on sympathetic activity, but this only occurs when there are sudden large changes in salt intake and, thereby, large changes in extracellular volume. It does not occur with modest salt reduction over a long period of time (7).\u003C\/p\u003E\n\u003Cp\u003EGraudal and J\u00fcrgens claim that salt reduction has adverse effects on blood lipids (2). However, these changes only occurred in their meta-analysis with acute and large reductions in salt intake, where there is a contraction in plasma volume and, thereby, a small increase in the concentration of lipids. Our meta-analysis clearly demonstrated that there were no significant changes in lipid levels (1). Indeed, Graudal and J\u00fcrgens\u2019s own meta-analysis, when they only considered studies of more than 4 weeks, showed no significant change in lipids, although in their paper they tried to imply that these were of borderline significance, which they were not. \u003C\/p\u003E\n\u003Cp\u003EGraudal and J\u00fcrgens continue to believe that there is a J-shaped association between salt intake and mortality. However, close examination of these studies shows that nearly all of them were done in patients who had severe cardiovascular disease or other diseases and were on multiple drug therapy. A careful analysis by the American Heart Association (8) concluded that these studies have many methodological flaws e.g. measurement error in assessing daily salt intake such as the use of spot urines which are notoriously inaccurate in measuring salt intake, other confounding factors not controlled for, and reverse causality, i.e. patients who are ill do not eat as much and therefore have a lower salt intake, but because of their illness, they are more likely to die. \u003C\/p\u003E\n\u003Cp\u003EFinally, Graudal and J\u00fcrgens make the astonishing claim that the benefits of salt reduction on cardiovascular disease is based on \u0022unproven blood pressure hypothesis\u0022. This claim is incorrect. Firstly, blood pressure throughout the range starting from 115\/75 mmHg is a major cause of cardiovascular disease (5), responsible for 62% of all strokes and 49% of coronary heart disease (9). Secondly, there is evidence from both prospective cohort studies (10) and, importantly, outcome trials (11) that a lower salt intake is related to a reduced risk of cardiovascular disease. For example, a recent meta-analysis of outcome trials demonstrated a significant reduction in cardiovascular events by 20% (P\u003C0.05) in spite of only a small reduction in salt intake of 2.0-2.3 g\/d (11). Unsurprisingly, Graudal and J\u00fcrgens choose to ignore such evidence.\u003C\/p\u003E\n\u003Cp\u003EThe totality of evidence for a causal relationship of chronic high salt intake with raised blood pressure and cardiovascular disease is very strong (12). The question now is not \u2018should\u2019 we reduce salt intake, but \u2018how\u2019 to do it. Many countries are now adopting a policy of reducing salt intake, and indeed the UK is leading the world with a structured, coherent salt reduction policy by getting the food industry to slowly take out the excessive amounts of salt in food. A reduction in population salt intake will have major beneficial effects, firstly by reducing blood pressure in the whole population (1,13) and by reducing cancer of the stomach (14), and it is likely that it will have a beneficial effect on bone demineralisation (15,16). Many studies have demonstrated major cost savings in all countries around the world with salt reduction (17-19). Indeed, it is one of the most cost-effective public health policies. \u003C\/p\u003E\n\u003Cp\u003EReferences\u003C\/p\u003E\n\u003Cp\u003E1. He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ 2013;346:f1325.\u003C\/p\u003E\n\u003Cp\u003E2. Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens 2012;25:1-15.\u003C\/p\u003E\n\u003Cp\u003E3. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ. Selected major risk factors and global and regional burden of disease. Lancet 2002;360:1347-60.\u003C\/p\u003E\n\u003Cp\u003E4. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2224-60.\u003C\/p\u003E\n\u003Cp\u003E5. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-193.\u003C\/p\u003E\n\u003Cp\u003E6. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-97.\u003C\/p\u003E\n\u003Cp\u003E7. Beckmann SL, Os I, Kjeldsen SE, Eide IK, Westheim AS, Hjermann I. Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension. Am J Hypertens 1995;8:704-11.\u003C\/p\u003E\n\u003Cp\u003E8. Whelton PK, Appel LJ, Sacco RL, Anderson CA, Antman EM, Campbell N, et al. Sodium, blood pressure, and cardiovascular disease: further evidence supporting the American Heart Association sodium reduction recommendations. Circulation 2012;126:2880-9.\u003C\/p\u003E\n\u003Cp\u003E9. World Health Report 2002: Reducing risks, promoting healthy life. Geneva, Switzerland: World Health Organisation, 2002. www.who.int\/whr\/2002.\u003C\/p\u003E\n\u003Cp\u003E10. Strazzullo P, D\u0027Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 2009;339:b4567\u003Cbr \/\u003E\n11. He FJ, MacGregor GA. Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials. Lancet 2011;378:380-2.\u003C\/p\u003E\n\u003Cp\u003E12. He FJ, MacGregor GA. Reducing population salt intake worldwide: from evidence to implementation. Prog Cardiovasc Dis 2010;52:363-82.\u003C\/p\u003E\n\u003Cp\u003E13. Aburto NJ, Ziolkovska A, Hooper L, Elliott P, Cappuccio FP, Meerpohl JJ. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ 2013;346:f1326.\u003C\/p\u003E\n\u003Cp\u003E14. D\u0027Elia L, Rossi G, Ippolito R, Cappuccio FP, Strazzullo P. Habitual salt intake and risk of gastric cancer: A meta-analysis of prospective studies. Clin Nutr 2012;31:489-98.\u003C\/p\u003E\n\u003Cp\u003E15. Cappuccio FP, Kalaitzidis R, Duneclift S, Eastwood JB. Unravelling the links between calcium excretion, salt intake, hypertension, kidney stones and bone metabolism. J Nephrol 2000;13:169-77.\u003C\/p\u003E\n\u003Cp\u003E16. Devine A, Criddle RA, Dick IM, Kerr DA, Prince RL. A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women. Am J Clin Nutr 1995;62:740-5.\u003C\/p\u003E\n\u003Cp\u003E17. Asaria P, Chisholm D, Mathers C, Ezzati M, Beaglehole R. Chronic disease prevention: health effects and financial costs of strategies to reduce salt intake and control tobacco use. Lancet 2007;370:2044-53.\u003C\/p\u003E\n\u003Cp\u003E18. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010;362:590-9.\u003C\/p\u003E\n\u003Cp\u003E19. National Institute for Health and Clinical Excellence (NICE). Guidance on the prevention of cardiovascular disease at the population level. \u003Ca href=\u0022http:\/\/guidance.nice.org.uk\/PH25\u0022\u003Ehttp:\/\/guidance.nice.org.uk\/PH25\u003C\/a\u003E. \u003C\/p\u003E\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-competing\u0022\u003E\r\n \u003Cp\u003E\u003Cstrong\u003ECompeting interests: \u003C\/strong\u003E\r\n Feng He is a member of Consensus Action on Salt \u0026amp; Health (CASH) and World Action on Salt \u0026amp; Health (WASH). Both CASH and WASH are nonprofit charitable organisations and Feng He does not receive any financial support from CASH or WASH. Graham MacGregor is board member of World Hypertension League (WHL), Chairman of Blood Pressure Association (BPA), Chairman of Consensus Action on Salt \u0026amp; Health (CASH) and Chairman of World Action on Salt \u0026amp; Health (WASH). WHL, BPA, CASH and WASH are nonprofit charitable organisations. Graham MacGregor does not receive any financial support from any of these organisations. \u003C\/p\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \u003C\/div\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-right-column\u0022 class=\u0022\u0022\u003E\r\n \u003Cdiv class=\u0022response-date\u0022\u003E\r\n \u003Cstrong\u003E17 April 2013\u003C\/strong\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-author\u0022\u003E\r\n Feng J He \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-occupation\u0022\u003E\r\n Senior Research Fellow \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-other_authors\u0022\u003E\r\n Graham A MacGregor \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-affiliation\u0022\u003E\r\n Queen Mary University of London \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-address\u0022\u003E\r\n Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ. \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022twitter-address\u0022\u003E\r\n \u003Ca href=\u0022https:\/\/twitter.com\/\u0022\u003E\u003C\/a\u003E \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-links\u0022\u003E\r\n\r\n \r\n \r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-separator\u0022 class=\u0022clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022light-grey-line\u0022\u003E\u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n\u003C\/div\u003E\r\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-row views-row-3 views-row-odd\u0022\u003E\n \r\n\u003Cdiv class=\u0022node node-highwire-comment clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022row rr-header\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022rr-left-column\u0022 class=\u0022\u0022\u003E\r\n\r\n \r\n \u003Cdiv class=\u0022response-title\u0022\u003E\r\n \u003Ca href=\u0022\/content\/346\/bmj.f1325\/rr\/641052\u0022\u003E\u003Ch3\u003ERe: Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials\u003C\/h3\u003E\r\n \u003C\/a\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \r\n \r\n \u003Cdiv class=\u0022content\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022response-body\u0022\u003E\r\n \u003Cp\u003EJust like other work on salt, this article is unconvincing. The evidence for salt causing any harm is extremely flimsy. I would like to draw readers\u2019 attention to the work of Gary Taubes on this subject (1, 2). He is a journalist who specialises in exposing bad science. He has reviewed all the literature on salt and interviewed many of the researchers. It is clearly demonstrated that salt is harmless.\u003C\/p\u003E\n\u003Cp\u003EReferences:\u003C\/p\u003E\n\u003Cp\u003E1. The (Political) Science of Salt. Science 14 August 1998: Vol. 281 no. 5379 pp. 898-907. \u003Ca href=\u0022http:\/\/www.sciencemag.org\/content\/281\/5379\/898.short\u0022\u003Ehttp:\/\/www.sciencemag.org\/content\/281\/5379\/898.short\u003C\/a\u003E\u003Cbr \/\u003E\n2. Salt, We Misjudged You. New York Times. 2 June 2012. \u003Ca href=\u0022http:\/\/www.nytimes.com\/2012\/06\/03\/opinion\/sunday\/we-only-think-we-know-the-truth-about-salt.html?pagewanted=all\u0022\u003Ehttp:\/\/www.nytimes.com\/2012\/06\/03\/opinion\/sunday\/we-only-think-we-know-t...\u003C\/a\u003E\u003C\/p\u003E\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-competing\u0022\u003E\r\n \u003Cp\u003E\u003Cstrong\u003ECompeting interests: \u003C\/strong\u003E\r\n No competing interests\u003C\/p\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \u003C\/div\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-right-column\u0022 class=\u0022\u0022\u003E\r\n \u003Cdiv class=\u0022response-date\u0022\u003E\r\n \u003Cstrong\u003E15 April 2013\u003C\/strong\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-author\u0022\u003E\r\n William Neville \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-occupation\u0022\u003E\r\n General Practitioner \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-other_authors\u0022\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-affiliation\u0022\u003E\r\n none \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-address\u0022\u003E\r\n Abbey Road Surgery, 63 Abbey Road, Waltham Cross, Hertfordshire, EN8 7LJ \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022twitter-address\u0022\u003E\r\n \u003Ca href=\u0022https:\/\/twitter.com\/\u0022\u003E\u003C\/a\u003E \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-links\u0022\u003E\r\n\r\n \r\n \r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-separator\u0022 class=\u0022clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022light-grey-line\u0022\u003E\u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n\u003C\/div\u003E\r\n \u003C\/div\u003E\n \u003Cdiv class=\u0022views-row views-row-4 views-row-even views-row-last\u0022\u003E\n \r\n\u003Cdiv class=\u0022node node-highwire-comment clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022row rr-header\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022rr-left-column\u0022 class=\u0022\u0022\u003E\r\n\r\n \r\n \u003Cdiv class=\u0022response-title\u0022\u003E\r\n \u003Ca href=\u0022\/content\/346\/bmj.f1325\/rr\/640806\u0022\u003E\u003Ch3\u003ERe: Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials\u003C\/h3\u003E\r\n \u003C\/a\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \r\n \r\n \u003Cdiv class=\u0022content\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022response-body\u0022\u003E\r\n \u003Cp\u003E\nIn their recently published meta-analysis (1), He et al. compares their analysis with ours (2). In contrast to the claim by He et al, the main difference between the two analyses is not the result of the outcomes, but the interpretation of the outcomes.\u003C\/p\u003E\n\u003Cp\u003EIn 1998 we published a meta-analysis including 83 references on the effect of sodium reduction, which analyzed other outcome variables than blood pressure (2). Requested by the Cochrane institution we have updated our analysis in 2003 (96 references) (3) and 2011 (167 references) (4). \u003C\/p\u003E\n\u003Cp\u003EEach of our analyses have been followed by a similar meta-analysis by He and MacGregor, being copies with respect to outcomes and extracted data, but with more restrictive inclusion criteria on study duration and dose of sodium reduction. The first was published in 2002 (25 references) (5). The second was published also as a Cochrane review (28 references) (6). It is, however, surprising that the editors of BMJ have chosen to give a high priority (15 pages) to a third copy by He et al. with a minimal update of 2 references and no news value (1).\u003C\/p\u003E\n\u003Cp\u003EHe et al. only include studies lasting 4 weeks or longer and with no additional treatment in any of the randomized groups. They argue that this makes a difference. It does concerning the power of the analysis (30 references vs. 167 references), but not convincingly concerning the outcomes. They find the effect on the blood pressure in hypertensive whites to be \u22125.12 mm Hg\/ \u22122.66 mm Hg, which is similar to our finding in studies lasting more than 4 weeks (-5.18\/-2.59). Although the effect on the blood pressure in normotensive whites was a little big bigger than our estimate, the difference between the two analyses was still small (-2.11\/-0.88 vs. -1.29\/-0.45). Like in our analysis, He et al. also find statistically significant increases in renin, aldosterone and noradrenalin, but they do not find effects on the lipids, which we also did not in studies lasting 4 weeks or more. However only 5-8 studies (262-365 participants) are included in the 4 lipid analyses, which have p-values between 0.11 and 0.22, indicating that the lack of significance could be due to lack of power. Consequently it is too early to decide whether the significant effect on lipids we found in 19-25 studies (586-773 participants) with duration of 1 week or more is temporary or permanent.\u003C\/p\u003E\n\u003Cp\u003EIn their conclusion He et al. link the association between blood pressure and mortality and between sodium reduction and blood pressure to conclude that sodium reduction is associated with mortality. This is, however, a hypothesis not proven by scientific data. Such a link is not obligatory, as exemplified by the effect of beta blockers, which reduce blood pressure in hypertensives twice as much as sodium reduction, but do not reduce mortality in a meta-analysis of 23613 participants (7). The reason for this is unknown, but could be side effects. However, in spite of the significant side effects on hormones and borderline significant trends on lipids in their own analysis, He et al. explains away this possibility and they also denies the possibility of a J-shaped association between salt intake and mortality shown in several recent population studies. Instead they rely completely on the unproven blood pressure hypothesis. With these firm beliefs He et al. can - in their copy paper \u2013 repeat unjustified conclusions from innumerable previous papers.\u003Cbr \/\u003E\nIn contrast, we think that general recommendations based on one single outcome (a small blood pressure effect) without knowing the consequences of this effect and possible accompanying side effects on morbidity and mortality is potentially hazardous.\u003C\/p\u003E\n\u003Cp\u003E1)\tHe FJ, Li L, MacGregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ 2013;346:f1325 doi: 10.1136\/bmj.f1325\u003C\/p\u003E\n\u003Cp\u003E2)\tGraudal NA, Gall\u00f8e AM, Garred P. Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a metaanalysis. JAMA 1998; 279:1383\u20131391.\u003C\/p\u003E\n\u003Cp\u003E3)\tJ\u00fcrgens G, Graudal NA.Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride. Cochrane Database Syst Rev. 2003;(1):CD004022.\u003C\/p\u003E\n\u003Cp\u003E4)\tGraudal NA, Hubeck-Graudal T, Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure, renin,aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Syst Rev. 2011 Nov 9; (11):CD004022. doi:10.1002\/14651858.CD004022.pub3.\u003C\/p\u003E\n\u003Cp\u003E5)\tHe FJ, MacGregor GA. Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health. J Hum Hypertens. 2002;16:761-70.\u003C\/p\u003E\n\u003Cp\u003E6)\tHe FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004937. DOI: 10.1002\/14651858.CD004937.\u003C\/p\u003E\n\u003Cp\u003E7)\tWiysonge CS, Bradley HA, Volmink J, Mayosi BM, Mbewu A, Opie LH. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2012 Nov 14;11:CD002003. doi:10.1002\/14651858.CD002003.pub4.\u003C\/p\u003E\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-competing\u0022\u003E\r\n \u003Cp\u003E\u003Cstrong\u003ECompeting interests: \u003C\/strong\u003E\r\n No competing interests\u003C\/p\u003E\r\n \u003C\/div\u003E\r\n\r\n \r\n \u003C\/div\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-right-column\u0022 class=\u0022\u0022\u003E\r\n \u003Cdiv class=\u0022response-date\u0022\u003E\r\n \u003Cstrong\u003E13 April 2013\u003C\/strong\u003E\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-author\u0022\u003E\r\n Niels Graudal \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-occupation\u0022\u003E\r\n Consultant \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-other_authors\u0022\u003E\r\n Gesche J\u00fcrgens \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-affiliation\u0022\u003E\r\n Copenhagen University Hospital, Rigshospitalet Rigshospitalet \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-address\u0022\u003E\r\n Blegdamsvej 9, DK-2100 Copenhagen \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022twitter-address\u0022\u003E\r\n \u003Ca href=\u0022https:\/\/twitter.com\/\u0022\u003E\u003C\/a\u003E \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022response-links\u0022\u003E\r\n\r\n \r\n \r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003Cdiv class=\u0022rr-separator\u0022 class=\u0022clearfix\u0022\u003E\r\n\r\n \u003Cdiv class=\u0022light-grey-line\u0022\u003E\u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n \u003C\/div\u003E\r\n\r\n\u003C\/div\u003E\r\n \u003C\/div\u003E\n \u003C\/div\u003E\n \n \n \n \n \n \n\u003C\/div\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003C\/body\u003E\u003C\/html\u003E"}